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I have developed mouse pharmacogenetic models for dependence on ethanol by selectively breeding lines of mice resistant, or susceptible, to the severity of withdrawal from ethanol dependence. With my collaborators I am analyzing the neurobiological mechanisms underlying the large differences between the Withdrawal Seizure-Prone and -Resistant lines. These studies are concentrated on the genetic and neuropharmacological mechanisms leading to alcohol withdrawal convulsions, on their differential susceptibility to other drugs of abuse, and on developing a more comprehensive set of behavioral assays characterizing withdrawal severity.
Other approaches include studies of multiple inbred strains of mice examining the basis for genetic correlations between susceptibilities to effects of different drugs of abuse. These studies have explored the specificity of genetic influences across different environments, including multiple laboratories. They are also intended to elucidate gene-environment interactions. Strain patterns of sensitivity sometimes indicate the important influence of single genes on drug responses.
We are also developing new lines of mice selectively bred for binge Drinking in the Dark as a part of the Integrative Neuroscience Initiative on Alcoholism (INIA-West) consortium. These mice drink to the point of intoxication, reaching average blood levels higher than the legal driving limit. We are exploring the pharmacological characteristics of the neural circuitry underlying this drinking as well as the behavioral characteristics of these mice.
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GENES BRAIN AND BEHAVIORno. 1 (2024): e12875-e12875
Addiction Biologyno. 5 (2022): e13212-e13212
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